{"doi":"10.1002/ajh.25931","title":"Upper airway microbiome changes in children with sickle cell disease during vaso‐occlusive and acute chest syndrome episodes","abstract":"Sickle cell disease (SCD) results in numerous complications, including acute chest syndrome (ACS) and vaso-occlusive crises (VOC). Beginning in infancy, patients with SCD are exposed to prophylactic antibiotics to prevent invasive pneumococcal disease from functional asplenia. Furthermore, these children commonly receive empiric broad-spectrum antibiotics when they present with febrile illnesses. Note, ACS is a leading cause of morbidity and premature death in people with SCD. Treatment with broad-spectrum systemic antibiotics is recommended for all occurrences, despite limited studies on the true occurrence of bacterial infections in ACS. VOC episodes are the most common complication in children with SCD. While antibiotics are not routinely recommended for uncomplicated VOC, they may be given if patients are febrile. The link between microbiome alterations and disease pathogenesis is established in other chronic diseases (eg, cystic fibrosis), but it is unknown if microbiome alterations are linked with SCD complications. Further, frequent antibiotic exposures can cause antibiotic-resistant pathogens. Therefore, is important to investigate if microbiome alterations occur at baseline or during acute illnesses such as ACS or VOC, given the antibiotic exposure these children frequently receive. To address this deficit, we conducted a prospective, single center one-year study of children with SCD to describe their baseline upper airway microbial composition and explore changes in microbial composition that occur early in hospitalizations for ACS or VOC. We hypothesized that the upper airway microbiome would significantly change during ACS and VOC compared to baseline. Full methods are available in the online supplement. In brief, these data were collected as part of a prospective study to explore gene expression profiles among children with SCD hospitalized for VOC and ACS.1 Deep posterior oropharyngeal swabs for microbiome analysis were obtained at baseline and placed in RNA later (ThermoFisher, AM7020). Samples were recollected within 24 hours of a hospitalization for VOC or ACS during their year of study participation. After DNA isolation and quality checks, samples were submitted to the University of Illinois for high throughput sequencing for 16S rRNA gene using the 515F (GTGYCAGCMGCCGCGGTAA) and 926R (CCGTCAATTCMTTTRAGT) primer pair and Illumina MiSeq platform. Differential abundance was analyzed via Wilcoxon test with false discovery rate P value correction, with statistical significance set at P < .05. We enrolled 83 children, and 25 had at least one hospitalization for either ACS or VOC. Fourteen participants were excluded from matched baseline to hospitalization microbiome analysis, due to low total sequences (n = 2) or >30% contaminant sequences in the baseline or hospitalization sample (n = 12). The demographics of the hospitalized cohort with acceptable sequences are in Table S1. The full cohort baseline demographics have been previously reported.1 Average counts for the overall cohort's baseline microbial composition are in Table S2. Streptococcus was the most abundant taxa present on average in all baseline samples, followed by Veillonella, Acinetobacter, Delftia, and Neisseria. Streptococcus, Veillonella and Neisseria predominance were similar to prior oropharynx microbiome studies in healthy children,2 although limited data on racially-matched children is available. We then compared the oropharyngeal microbiomes of children with SCD at baseline to early during their hospitalization for either a VOC (n = 6) or ACS (n = 5) episode. There were no baseline differences in α-diversity or β-diversity between children who were hospitalized for ACS or VOC and children not hospitalized. Compared to their baseline, children admitted for VOC experienced no changes in bacterial α-diversity (total ASVs, Pielou's evenness, Faith's, and Shannon), but demonstrated altered bacterial β-diversity of total bacterial populations as mea","journal":"American Journal of Hematology","year":2020,"id":109238,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":494733,"name":"Chandra L. Shrestha","orcid":null,"position":1,"is_corresponding":false},{"id":522680,"name":"Kavitha Kotha","orcid":null,"position":2,"is_corresponding":false},{"id":522681,"name":"Abena Minta","orcid":null,"position":3,"is_corresponding":false},{"id":242930,"name":"Shuzhong Zhang","orcid":"0000-0001-5838-1676","position":4,"is_corresponding":false},{"id":32980,"name":"Asunción Mejías","orcid":"0000-0002-5983-8006","position":5,"is_corresponding":false},{"id":361952,"name":"Michael T. Bailey","orcid":"0000-0002-2222-3980","position":6,"is_corresponding":false},{"id":320799,"name":"Susan E. Creary","orcid":"0000-0002-4730-8139","position":7,"is_corresponding":false},{"id":493781,"name":"Benjamin T. Kopp","orcid":"0000-0002-2021-7990","position":8,"is_corresponding":false},{"id":493780,"name":"Brett R. Loman","orcid":"0000-0001-8830-7506","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-18T23:12:50.712357Z","pmid":"32644239","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}